Abstract
Cellular inhibitor of apoptosis protein (cIAP) 1 and cIAP2 set the balance between transcription factor and apoptosis signaling downstream of tumor necrosis factor (TNF) receptor superfamily members by acting as ubiquitin E3 ligases for substrates that are part of the TNF receptor complex. To fulfill this role, cIAPs must be recruited to the receptor complex by TNF-receptor-associated factor (TRAF) 2. In this study, we reconstituted the complex between baculoviral IAP repeat (BIR) 1 of cIAP1 and the coiled-coil region of TRAF2, solved the structure of BIR1 from cIAP1, and mapped key binding residues on each molecule using mutagenesis. Biophysical analysis indicates that a single BIR1 domain binds the trimeric TRAF2 coiled-coil domain. This suggests that only one IAP molecule binds to each TRAF trimer and makes it likely that the dimeric cIAPs crosslink two TRAF trimers.